Ia. Silver et M. Erecinska, GLUCOSE-INDUCED INTRACELLULAR ION CHANGES IN SUGAR-SENSITIVE HYPOTHALAMIC NEURONS, Journal of neurophysiology, 79(4), 1998, pp. 1733-1745
In the lateral hypothalamic area (LHA) of rat brain, similar to 30% of
cells showed sensitivity to small changes in local concentrations of
glucose. These ''glucose-sensitive'' neurons demonstrated four types o
f behavior, three of which probably represent segments of a continuous
spectrum of recruitment in response to ever more severe changes in bl
ood sugar. Type I cells showed maximum activity less than or equal to
5.6 mM blood glucose but became completely silent at hyperglycemia of
10-12 mM (normoglycemia 7.6 +/- 0.3 mM; mean +/- SD). Type II and In n
eurons exhibited a wider range of response. Type IV cells (5-7% of glu
cose-sensitive neurons) paralleled the behavior of sugar-sensitive cel
ls in ventromedial hypothalamic nucleus (VMH). In VMH, similar to 40%
of cells responded to changes in blood glucose over a range of concent
rations from 3.6 to 17 mM, by increasing their firing rate as sugar le
vel rose and vice versa. Ionic shifts during increases in blood (brain
) glucose levels were similar in LHA types I-III but fastest in I and
slowest in III. [Na+](i) fell by 5-9 mM, [K+](i) rose by 6-8 mM, and p
lasma membrane hyperpolarized by 5 mV. [Ca2+](i) declined by 15-20 nM
in line with membrane hyperpolarization. In VMH and type IV LHA cells,
[K+](i) fell 3-8 mM and plasma membrane depolarized -3 to -5 mV as bl
ood/brain glucose concentration increased from 7.6/2.4 to 17.6/4.2 mM,
whereas [Ca2+](i) increased from 125 to 180 nM as a consequence of fa
lling membrane potential. During falls in blood/brain sugar concentrat
ion the effects in both VMH and LHA cells were reversed. The findings
are consistent with the ionic shifts in types I-III LHA cells being de
pendent on alterations in Na/K-ATPase activity, whereas those in VMH a
nd type IV LHA cells could be caused by modulation of ATP-dependent K channels. A possible mechanism for linking the effects of small chang
es in glucose to ATP generation, which could bring about the above phe
nomena, is the interposition of a ''glucokinase-type'' enzyme in a rol
e similar to that which it has in glucose-sensing pancreatic beta-cell
s.